This invention relates to a chemical (i.e., non-enzymatic) process for deacylating N-acyl-6-substituted-2-[2-aminoethylthio]-1-carbadethiapen-2-em-3-carboxyl ic acids (I); such acylated species (I) and corresponding deacylated forms are antibiotics: ##STR1## wherein R is, inter alia, hydroxyl substituted alkyl and R.degree. is acyl. The most well known members of the series defined by structure I are the thienamycins wherein R is 1-hydroxyethyl and R.degree. is acetyl; such products (1) are natural products of fermentation and are known: ##STR2## Species classified under sub-category (1) are alternatively known by the following nomenclature and are disclosed and claimed in the following co-pending, U.S. patent applications:
1. N-acyl thienamycin--U.S. patent application Ser. No. 827,503 (Aug. 25, 1977); and PA0 2. 890A.sub.1 and 890A.sub.3 --U.S. patent application Ser. No. 827,504 (Aug. 25, 1977) now U.S. Pat. No. 4,162,324, issued July 24, 1979 which applications are incorporated herein by reference.
A second sub-category (2) under generic structure I comprises sulfate esters of the carbinol which are natural products of fermentation and which bear the N-acetyl group: ##STR3## The species of sub-category 2 are known and are described and claimed in U.S. patent applications Ser. No. 860,662 (Dec. 15, 1977) now abandoned, in favor of U.S. Ser. No. 006,959, filed Jan. 25, 1979 and Ser. No. 891,799 (Mar. 30, 1978) which are incorporated herein by reference.
The third sub-category under generic structure I includes the 6-ethyl species (3): ##STR4## R.degree. is acyl as defined above.
Species 3 is known (R.degree.=acetyl) and available to the art; see the Journal of Antibiotics, Volume 31, No. 5, pages 480-482 (May 1978); such species and deacylated species are disclosed and claimed in co-pending, commonly assigned U.S. patent applications Ser. No. 861,230 (Dec. 16, 1977) now abandoned, in favor of U.S. Ser. No. 048,944, filed June 15, 1979 and 843,378 (Oct. 19, 1977) now abandoned in favor of its continuation-in-part U.S. Ser. No. 933,681 filed Aug. 17, 1978 which are incorporated herein by reference.
Finally, a fourth category (4) embraces the balance of products prepared by fermentation and those obtained by processes of total synthesis; category 4 is actually broader and more general than I. These compounds (4) are most conveniently represented by structure (I) above, but, in the most general case, are represented by structure 4: ##STR5##
With respect to 4, R.sup.1 and R.sup.2 are, inter alia, independently selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, aralkyl, aryl, alkenyl and the like and R.sup.3 is a similarly broadly defined radical which is characterized for purposes of this process by having an amino group which is acylated. Such compounds 4 are disclosed and claimed in U.S. patent application Ser. No. 861,247 (Dec. 16, 1977); 843,378 (Oct. 19, 1977) now abandoned, in favor of U.S. Ser. No. 933,681, filed Aug. 17, 1978; 843,375 (Oct. 19, 1977); and 843,171 (Oct. 19, 1977); which are incorporated herein by reference.
The N-acyl species defined above I which includes the sub-categories 1, 2 and 3 and the generalized form 4 are all antibiotics. The species obtained by fermentation usually have acetyl as the acyl group; whereas those obtained by total synthesis are not limited to acetyl and may have any value for the acyl group. It is desirable, however, to have a process for obtaining the free amino compound since the deacylated species usually demonstrates enhanced antibiotic activity. Also, the deacylated antibiotic may also be regarded as an intermediate for subsequent derivatization of the amino group; such derivatization processes, however, are not embraced by the present invention.